1my7
From Proteopedia
(New page: 200px<br /><applet load="1my7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1my7, resolution 1.49Å" /> '''NF-kappaB p65 subuni...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1my7.gif|left|200px]]<br /><applet load="1my7" size=" | + | [[Image:1my7.gif|left|200px]]<br /><applet load="1my7" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1my7, resolution 1.49Å" /> | caption="1my7, resolution 1.49Å" /> | ||
'''NF-kappaB p65 subunit dimerization domain homodimer N202R mutation'''<br /> | '''NF-kappaB p65 subunit dimerization domain homodimer N202R mutation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | IkappaBalpha inhibits transcription factor NF-kappaB activity by specific | + | IkappaBalpha inhibits transcription factor NF-kappaB activity by specific binding to NF-kappaB heterodimers composed of p65 and p50 subunits. It binds with slightly lower affinity to p65 homodimers and with significantly lower affinity to homodimers of p50. We have employed a structure-based mutagenesis approach coupled with protein-protein interaction assays to determine the source of this dimer selectivity exhibited by IkappaBalpha. Mutation of amino acid residues in IkappaBalpha that contact NF-kappaB only marginally affects complex binding affinity, indicating a lack of hot spots in NF-kappaB/IkappaBalpha complex formation. Conversion of the weak binding NF-kappaB p50 homodimer into a high affinity binding partner of IkappaBalpha requires transfer of both the NLS polypeptide and amino acid residues Asn202 and Ser203 from the NF-kappaB p65 subunit. Involvement of Asn202 and Ser203 in complex formation is surprising as these amino acid residues occupy solvent exposed positions at a distance of 20A from IkappaBalpha in the crystal structures. However, the same amino acid residue positions have been genetically isolated as determinants of binding specificity in a homologous system in Drosophila. X-ray crystallographic and solvent accessibility experiments suggest that these solvent-exposed amino acid residues contribute to NF-kappaB/IkappaBalpha complex formation by modulating the NF-kappaB p65 subunit NLS polypeptide. |
==About this Structure== | ==About this Structure== | ||
| - | 1MY7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1MY7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MY7 OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ghosh, G.]] | [[Category: Ghosh, G.]] | ||
| - | [[Category: Huang, D | + | [[Category: Huang, D B.]] |
| - | [[Category: Hughes, C | + | [[Category: Hughes, C A.]] |
[[Category: Huxford, T.]] | [[Category: Huxford, T.]] | ||
| - | [[Category: Komives, E | + | [[Category: Komives, E A.]] |
[[Category: Mishler, D.]] | [[Category: Mishler, D.]] | ||
| - | [[Category: Phelps, C | + | [[Category: Phelps, C B.]] |
[[Category: Reeves, R.]] | [[Category: Reeves, R.]] | ||
| - | [[Category: Sengchanthalangsy, L | + | [[Category: Sengchanthalangsy, L L.]] |
[[Category: activator]] | [[Category: activator]] | ||
[[Category: beta-sandwich]] | [[Category: beta-sandwich]] | ||
| Line 32: | Line 32: | ||
[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:00:16 2008'' |
Revision as of 12:00, 21 February 2008
|
NF-kappaB p65 subunit dimerization domain homodimer N202R mutation
Overview
IkappaBalpha inhibits transcription factor NF-kappaB activity by specific binding to NF-kappaB heterodimers composed of p65 and p50 subunits. It binds with slightly lower affinity to p65 homodimers and with significantly lower affinity to homodimers of p50. We have employed a structure-based mutagenesis approach coupled with protein-protein interaction assays to determine the source of this dimer selectivity exhibited by IkappaBalpha. Mutation of amino acid residues in IkappaBalpha that contact NF-kappaB only marginally affects complex binding affinity, indicating a lack of hot spots in NF-kappaB/IkappaBalpha complex formation. Conversion of the weak binding NF-kappaB p50 homodimer into a high affinity binding partner of IkappaBalpha requires transfer of both the NLS polypeptide and amino acid residues Asn202 and Ser203 from the NF-kappaB p65 subunit. Involvement of Asn202 and Ser203 in complex formation is surprising as these amino acid residues occupy solvent exposed positions at a distance of 20A from IkappaBalpha in the crystal structures. However, the same amino acid residue positions have been genetically isolated as determinants of binding specificity in a homologous system in Drosophila. X-ray crystallographic and solvent accessibility experiments suggest that these solvent-exposed amino acid residues contribute to NF-kappaB/IkappaBalpha complex formation by modulating the NF-kappaB p65 subunit NLS polypeptide.
About this Structure
1MY7 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Solvent exposed non-contacting amino acids play a critical role in NF-kappaB/IkappaBalpha complex formation., Huxford T, Mishler D, Phelps CB, Huang DB, Sengchanthalangsy LL, Reeves R, Hughes CA, Komives EA, Ghosh G, J Mol Biol. 2002 Dec 6;324(4):587-97. PMID:12460563
Page seeded by OCA on Thu Feb 21 14:00:16 2008
Categories: Mus musculus | Single protein | Ghosh, G. | Huang, D B. | Hughes, C A. | Huxford, T. | Komives, E A. | Mishler, D. | Phelps, C B. | Reeves, R. | Sengchanthalangsy, L L. | Activator | Beta-sandwich | Beta-sheet | Homodimerdna-binding | Ig | Immunoglobulin | Nuclear protein | Phosphorylation | Transcription regulation
